The protests began about five minutes into the speech and continued until his closing lines nearly 45 minutes later, as different individuals and groups -- strategically placed in different locations all around the more than 7,000-person capacity auditorium -- caused disturbances with signs and chants.
Several of the protesters were connected to Black Lives Matter, either wearing clothing bearing the movement's name or chanting "black lives matter."
Other signs called out Trump's rhetoric, saying "Stop the hate, we make America great."
Each time, the crowd booed and the protesters were quickly removed by a combination of security and authorities, though Trump grew clearly more frustrated as the disruptions continued.
"The dishonest media ... will make that one person into the headline," he said after the first one.
Trump has faced protests throughout his campaign, mainly aimed at his rhetoric about immigrants and foreigners, including from Black Lives Matter, but thus far the protests at each event have only caused one or two disturbances.
On Friday night Trump continued his recent effort to urge care with protesters after an Alabama rally last month in which a Black Lives Matter protester was roughed up by the crowd.
"Make sure that young lady is in beautiful shape," Trump said after the first interruption.
But by the later interruptions, he urged security to deal with the individuals more quickly.
"Why don't you take them out the nearest door instead of walking them through the whole place?" he said after the eighth incident.
He also blamed the frustration the Black Lives Matter protesters feel on President Barack Obama, saying instead of a "cheerleader" Obama has been a "great divider."
The GOP front-runner also said he thought he could convince the protesters to join his cause.
"If I could speak to these four people, I'd say, 'Look, you may be a Democrat, you may be a liberal, who cares, we're going to make our country strong, we're going to make it good," Trump said. "I really think I could talk sense into them. ... But remember there's only four people."
The mogul diligently continued with his speech through each interruption, but the rally was on the shorter end of his usual length and he began taking questions from the audience much earlier in his event than typical.
According to Wake County Sheriff Donnie Harrison, the authorities removed about 25 protesters from the event. Western Wake Fire Rescue Capt. Brian Egan said the capacity crowd numbered about 7,800.
While most of the protesters were peacefully removed, on two occasions apparent veterans wearing fatigues were observed forcefully manhandling protesters in an attempt to remove them, until authorities took over.
One self-identified protester tweeted about being violently removed.
"Forcibly removed from #trump rally. Trump supporters kicked me, grabbed my neck, pushed me, and more all while security jacks me up. Awful," Romain Stanley tweeted.
Stanley told CNN via Twitter he was escorted off the property.
No arrests were made, according to Harrison.
"To my knowledge, we didn't arrest anybody, we just escorted them out," he said, adding the only goal was to "keep it peaceful."
A combination of the Wake County Sheriff Department, Secret Service, Trump security, North Carolina State Fairgrounds Police and Highway Patrol were working the event according to Harrison.